Enantioseparation of paroxetine intermediate on an amylose-derived chiral stationary phase by supercritical fluid chromatography.
Enantioseparation of paroxetine intermediate on an amylose-derived chiral stationary phase by supercritical fluid chromatography.
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DOI：
10.1016/j.chroma.2009.04.069
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
Bao-gen Su;Zongbi Bao;Huabin Xing;Yiwen Yang;Qilong Ren
中科院分区：
文献类型：
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作者：
Bao-gen Su;Zongbi Bao;Huabin Xing;Yiwen Yang;Qilong Ren
研究了反式-（-）-帕罗西汀的重要外消旋前体之一反式-3-乙氧羰基-4-（4′-氟苯基）-1-甲基哌啶-2，6-二酮（3）在Daicel Chiralpak AD柱上的超临界流体色谱拆分。以甲醇、乙醇和异丙醇修饰的超临界CO2为移动的流动相。考察了醇类改性剂的种类和浓度对保留因子、对映选择性和分离度的影响。在甲醇、乙醇和异丙醇中，异丙醇是最好的改进剂，当异丙醇浓度为9.5%（v/v）时，外消旋体3的分离度为15.86，保留因子为6.323。在压力为12- 24 MPa、温度为303.15-318.15K、异丙醇体积分数为9.5%的条件下，考察了压力和温度对反应的影响。结果表明，较低的压力和温度有利于手性拆分。利用van 't霍夫图计算了异构体的异构选择性温度为410 K。在实验条件下，对映体分离过程是“手性驱动”的。最后用简化的格子流体模型对保留因子进行了关联，两种对映体的平均绝对相对偏差（AARD%）均小于1.76%。
The enantioseparation of trans-3-ethoxycarbonyl-4-(4′-fluorophenyl)-1-methyl piperidine-2,6-dione (3), which is one of the important racemic precursors of trans-(−)-paroxetine, has been investigated using supercritical fluid chromatography on a Daicel Chiralpak AD column. Supercritical CO2modified with methanol, ethanol and 2-propanol were used as mobile phase. The influence of type and concentration of alcohol modifier on retention factor, enantioselectivity and resolution were studied. Among methanol, ethanol and 2-propanol, 2-propanol was proved to be the most favorable modifier, and 9.5% (v/v) of 2-propanol was the preferred concentration at which racemate 3 could be separated with resolution of 15.86 and retention factor of 6.323. The effects of pressure and temperature were investigated at 9.5% (v/v) of 2-propanol in the pressure range of 12–24MPa and temperature range of 303.15–318.15K. It was found that the lower pressure and temperature were favorable to the enantioseparation. Using van’t Hoff plot, the isoenantioselective temperature was calculated to be 410K. The enantioseparation process was “enthalpically driven” under experimental conditions. Finally, the retention factors were satisfactorily correlated by a simplified lattice–fluid model with average absolute relative deviation (AARD%) of both enantiomers smaller than 1.76%.